BioPAX pathway converted from "Activation of the pre-replicative complex" in the Reactome database.Activation of the pre-replicative complexActivation of the pre-replicative complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101886741nucleoplasmGO0005654pre-replicative complex [nucleoplasm]pre-replicative complexReactome DB_ID: 101886441CDT1:CDC6:ORC:origin complex [nucleoplasm]CDT1:CDC6:ORC:origin complexReactome DB_ID: 101883891CDC6:ORC:origin complex [nucleoplasm]CDC6:ORC:origin complexReactome DB_ID: 101883871ORC:origin of replication [nucleoplasm]ORC:origin of replicationReactome DB_ID: 101883381UniProt:F1QRE0orc4Reactomehttp://www.reactome.orgDanio rerioNCBI Taxonomy7955UniProtF1QRE0Chain Coordinates1EQUAL436EQUALReactome DB_ID: 101883541UniProt:Q6ZM36orc6UniProtQ6ZM361EQUAL252EQUALReactome DB_ID: 101883461UniProt:A0A2R8QDP7orc1UniProtA0A2R8QDP71EQUAL861EQUALReactome DB_ID: 101883851Orc2 associated with MCM8 [nucleoplasm]Orc2 associated with MCM8Reactome DB_ID: 101883831UniProt:E7F643mcm8UniProtE7F6431EQUAL840EQUALReactome DB_ID: 101883201UniProt:A0A0R4IFI7orc2UniProtA0A0R4IFI71EQUAL577EQUALReactome Database ID Release 7510188385Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188385ReactomeR-DRE-1769701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-176970.1Reactome DB_ID: 101883301UniProt:Q6P0X9orc5UniProtQ6P0X91EQUAL435EQUALReactome DB_ID: 684191origin of replication [nucleoplasm]origin of replicationARSautonomously replicating sequenceoriginReactome DB_ID: 101883161UniProt:F1QP75orc3UniProtF1QP751EQUAL711EQUALReactome Database ID Release 7510188387Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188387ReactomeR-DRE-685401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68540.1Reactome DB_ID: 101883621UniProt:F1R1N7cdc6UniProtF1R1N71EQUAL560EQUALReactome Database ID Release 7510188389Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188389ReactomeR-DRE-685431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68543.1Reactome DB_ID: 101886421UniProt:E7F2R5cdt1UniProtE7F2R51EQUAL546EQUALReactome Database ID Release 7510188644Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188644ReactomeR-DRE-685441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68544.1Reactome DB_ID: 101886721MCM2-7 [nucleoplasm]MCM2-7Reactome DB_ID: 101886581UniProt:F1QK71mcm5UniProtF1QK711EQUAL734EQUALReactome DB_ID: 101886661UniProt:A0A0R4IF39mcm7UniProtA0A0R4IF392EQUAL719EQUALReactome DB_ID: 101886501UniProt:Q5RIC5mcm3UniProtQ5RIC52EQUAL808EQUALReactome DB_ID: 101886701UniProt:A0A0R4IF65mcm2UniProtA0A0R4IF652EQUAL904EQUALReactome DB_ID: 101886541UniProt:Q6NZV2mcm4UniProtQ6NZV22EQUAL863EQUALReactome DB_ID: 101886621UniProt:F1R5P3mcm6UniProtF1R5P31EQUAL821EQUALReactome Database ID Release 7510188672Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188672ReactomeR-DRE-685581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68558.1Reactome Database ID Release 7510188674Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188674ReactomeR-DRE-685591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68559.1Reactome DB_ID: 101887631UniProt:Q5RHY1mcm10UniProtQ5RHY11EQUAL875EQUALReactome DB_ID: 101887841MCM10:pre-replicative complex [nucleoplasm]MCM10:pre-replicative complexReactome DB_ID: 101886741Reactome DB_ID: 1018876311EQUAL875EQUALReactome Database ID Release 7510188784Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188784ReactomeR-DRE-685601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68560.1Reactome Database ID Release 7510188786Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188786ReactomeR-DRE-689191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68919.1MCM10 is required for human DNA replication. In S. cerevisiae, Mcm10, like Mcm2-7, is required for minichromosome maintenance, but Mcm10 has no sequence homology with these other proteins (Merchant et al., 1997). Genetic studies have demonstrated that Mcm10 is required for DNA replication in S. pombe (Aves et al., 1998) and S. cerevisiae cells (Homesley et al., 2000) and immunodepletion of XlMcm10 interferes with DNA replication in Xenopus egg extracts (Wohlschlegel et al., 2002). Human Mcm10 interacts with chromatin in G1 phase and then dissociates during G2 phase. In S. cerevisiae, Mcm10 has been shown to localize to origins during G1 (Ricke and Bielinsky, 2004), and it may stabilize the association of Mcm2-7 with the pre-replicative complex (Sawyer et al., 2004). This timing of association is consistent with studies that demonstrate that, in Xenopus egg extracts, Mcm10 is required for association of Cdc45, but not Mcm2-7 with chromatin. Biochemical evidence that Mcm10 plays a direct role in the activation of the pre-replicative complex includes the requirement for SpMcm10 in the phosphorylation of the Mcm2-7 complex by DDK (Lee et al., 2004) and the fact that SpMcm10 binds and stimulates DNA polymerase alpha activity (Fien et al., 2004).9154825Pubmed1997A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiaeMerchant, AMKawasaki, YChen, YLei, MTye, Bik KMol Cell Biol 17:3261-7110783164Pubmed2000Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins.Homesley, LLei, MKawasaki, YSawyer, SChristensen, TTye, Bik KGenes Dev 14:913-2614766746Pubmed2004Primer utilization by DNA polymerase alpha-primase is influenced by its interaction with Mcm10pFien, KCho, YSLee, JKRaychaudhuri, STappin, IHurwitz, JJ Biol Chem 279:16144-5315494305Pubmed2004Mcm10 regulates the stability and chromatin association of DNA polymerase-alphaRicke, RMBielinsky, AKMol Cell 16:173-8511282021Pubmed2001Initiating DNA synthesis: from recruiting to activating the MCM complex.Lei, MTye, Bik KJ Cell Sci 114:1447-5411095689Pubmed2000The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.Izumi, MYanagi, KMizuno, TYokoi, MKawasaki, YMoon, KYHurwitz, JYatagai, FHanaoka, FNucleic Acids Res 28:4769-779745018Pubmed1998The essential schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) geneAves, SJTongue, NFoster, AJHart, EACurr Genet 34:164-7112604790Pubmed2003The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinaseLee, JKSeo, YSHurwitz, JProc Natl Acad Sci U S A 100:2334-911864598Pubmed2002Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45.Wohlschlegel, JADhar, SKProkhorova, TADutta, AWalter, JCMol Cell 9:233-4015201046Pubmed2004Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiaeSawyer, SLCheng, IHChai, WTye, Bik KJ Mol Biol 340:195-202inferred by electronic annotationIEAGOIEACdt1 is displaced from the pre-replicative complex.Cdt1 is displaced from the pre-replicative complex.This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101887841Reactome DB_ID: 1018864211EQUAL546EQUALReactome DB_ID: 101887671MCM10:active pre-replicative complex [nucleoplasm]MCM10:active pre-replicative complexReactome DB_ID: 1018876311EQUAL875EQUALReactome DB_ID: 101887651active pre-replicative complex [nucleoplasm]active pre-replicative complexReactome DB_ID: 101883891Reactome DB_ID: 101886721Reactome Database ID Release 7510188765Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188765ReactomeR-DRE-1565621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156562.1Reactome Database ID Release 7510188767Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188767ReactomeR-DRE-1565641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156564.1Reactome Database ID Release 7510188788Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188788ReactomeR-DRE-689401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68940.1At the beginning of this reaction, 1 molecule of 'Mcm10:pre-replicative complex' is present. At the end of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', and 1 molecule of 'CDT1' are present.<br><br> This reaction takes place in the 'nucleus'.<br>12045100Pubmed2002DNA replication in eukaryotic cells.Bell, SPDutta, AAnnu Rev Biochem 71:333-74inferred by electronic annotationIEAGOIEACdt1 associates with gemininCdt1 associates with gemininThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 1018864211EQUAL546EQUALReactome DB_ID: 101892701UniProt:Q1LU98gmnnUniProtQ1LU981EQUAL209EQUALReactome DB_ID: 101892721Cdt1:geminin [nucleoplasm]Cdt1:gemininReactome DB_ID: 1018864211EQUAL546EQUALReactome DB_ID: 1018927011EQUAL209EQUALReactome Database ID Release 7510189272Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189272ReactomeR-DRE-1565021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156502.1Reactome Database ID Release 7510189274Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189274ReactomeR-DRE-692991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69299.1At the beginning of this reaction, 1 molecule of 'geminin', and 1 molecule of 'CDT1' are present. At the end of this reaction, 1 molecule of 'Cdt1:geminin' is present.<br><br> This reaction takes place in the 'nucleoplasm'.<br>11125146Pubmed2000Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.Wohlschlegel, JADwyer, BTDhar, SKCvetic, CWalter, JCDutta, AScience 290:2309-12inferred by electronic annotationIEAGOIEACDK and DDK associate with the Mcm10:pre-replicative complexCDK and DDK associate with the Mcm10:pre-replicative complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101887591DDK [nucleoplasm]DDKReactome DB_ID: 101887531UniProt:B0UYI0cdc7UniProtB0UYI01EQUAL574EQUALReactome DB_ID: 101887571UniProt:B5DDZ2dbf4UniProtB5DDZ21EQUAL674EQUALReactome Database ID Release 7510188759Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188759ReactomeR-DRE-683881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68388.1Reactome DB_ID: 101887671Reactome DB_ID: 101887491CDK [nucleoplasm]CDKReactome DB_ID: 101887471UniProt:Q7ZWB1cdk2UniProtQ7ZWB11EQUAL298EQUALReactome DB_ID: 101887431Ghost homologue of cyclin [nucleoplasm]Ghost homologue of cyclinReactome Database ID Release 7510188749Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188749ReactomeR-DRE-683801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68380.1Reactome DB_ID: 101887691CDK:DDK:MCM10:active pre-replicative complex [nucleoplasm]CDK:DDK:MCM10:active pre-replicative complexReactome DB_ID: 101887591Reactome DB_ID: 101887671Reactome DB_ID: 101887491Reactome Database ID Release 7510188769Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188769ReactomeR-DRE-685611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68561.1Reactome Database ID Release 7510188782Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188782ReactomeR-DRE-689181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68918.1At the beginning of this reaction, 1 molecule of 'Mcm10:active pre-replicative complex', 1 molecule of 'DDK', and 1 molecule of 'CDK' are present. At the end of this reaction, 1 molecule of 'CDK:DDK:Mcm10:pre-replicative complex' is present.<br><br> This reaction takes place in the 'nucleus'.<br>10523313Pubmed1999Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication.Jiang, WMcDonald, DHope, TJHunter, TonyEMBO J 18:5703-1310373557Pubmed1999A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.Kumagai, HSato, NYamada, MMahony, DSeghezzi, WLees, EArai, KMasai, HMol Cell Biol 19:5083-95inferred by electronic annotationIEAGOIEA2.7.10Mcm2-7 is phosphorylated by DDKMcm2-7 is phosphorylated by DDKThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101886721Reactome DB_ID: 293581ATP(4-) [ChEBI:30616]ATP(4-)Adenosine 5'-triphosphateatpATPChEBI30616Reactome DB_ID: 101888791p-MCM2-7 [nucleoplasm]p-MCM2-7Reactome DB_ID: 1135501hydrogenphosphate [ChEBI:43474]hydrogenphosphate[PO3(OH)](2-)HYDROGENPHOSPHATE IONhydrogen phosphate[P(OH)O3](2-)HPO4(2-)phosphateINORGANIC PHOSPHATE GROUPChEBI43474Reactome DB_ID: 101886721Reactome Database ID Release 7510188879Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188879ReactomeR-DRE-685691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68569.1Reactome DB_ID: 1135821ADP(3-) [ChEBI:456216]ADP(3-)ADP trianion5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADPChEBI456216PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10188759GO0004713GO molecular functionReactome Database ID Release 7510188880Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188880Reactome Database ID Release 7510188882Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188882ReactomeR-DRE-689541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68954.1At the beginning of this reaction, 1 molecule of 'Mcm2-7 complex', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phosphorylated Mcm2-7 complex', and 1 molecule of 'ADP' are present.<br><br> This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'DDK'.<br>10846177Pubmed2000Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a critical threonine residue of Cdc7 by Cdks.Masai, HMatsui, EYou, ZIshimi, YTamai, KArai, KJ Biol Chem 275:29042-52inferred by electronic annotationIEAGOIEACdc45 associates with the pre-replicative complex at the originCdc45 associates with the pre-replicative complex at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101887411UniProt:Q7ZU79cdc45UniProtQ7ZU791EQUAL566EQUALReactome DB_ID: 101887691Reactome DB_ID: 101887711CDK:DDK:MCM10:active pre-replicative complex:CDC45 [nucleoplasm]CDK:DDK:MCM10:active pre-replicative complex:CDC45Reactome DB_ID: 1018874111EQUAL566EQUALReactome DB_ID: 101887691Reactome Database ID Release 7510188771Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188771ReactomeR-DRE-685641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68564.1Reactome Database ID Release 7510188780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188780ReactomeR-DRE-689171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68917.1Once the Mcm2-7 complex has been assembled onto the origin of replication, the next step is the assembly of Cdc45, an essential replication protein, in late G1. The assembly of Cdc45 onto origins of replication forms a complex distinct from the pre-replicative complex, sometimes called the pre-initiation complex. The assembly of Cdc45 onto origins correlates with the time of initiation. Like the Mcm2-7 proteins, Cdc45 binds specifically to origins in the G1 phase of the cell cycle and then to non-origin DNA during S phase and is therefore thought to travel with the replication fork. Indeed, S. cerevisiae Cdc45 is required for DNA replication elongation as well as replication initiation. Cdc45 is required for the association of alpha DNA polymerase:primase with chromatin. Based on this observation and the observation that in S. cerevisiae, cCdc45 has been found in large complexes with some components of Mcm2-7 complex, it has been suggested that Cdc45 plays a scaffolding role at the replication fork, coupling Pol-alpha:primase to the replication fork through the helicase. Association of Cdc45 with origin DNA is regulated in the cell cycle and its association is dependent on the activity of cyclin-dependent kinases but not the Cdc7/Dbf4 kinase. In Xenopus egg extracts, association of Cdc45 with chromatin is dependent on Xmus101. TopBP1, the human homolog of Xmus1, is essential for DNA replication and interacts with DNA polymerase epsilon, one of the polymerases involved in replicating the genome. TopBP1 homologs have been found in S. cerevisiae and S. pombe. Sld3, an additional protein required for Cdc45 association with chromatin in S. cerevisiae and S. pombe, has no known human homolog.9554851Pubmed1998Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin.Zou, LStillman, BScience 280:593-611756551Pubmed2001A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival.Yamane, KWu, XChen, JMol Cell Biol 22:555-6612438414Pubmed2002The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication.Van Hatten, RATutter, AVHolway, AHKhederian, AMWalter, JCMichael, WMJ Cell Biol 159:541-79660782Pubmed1998The human homolog of Saccharomyces cerevisiae CDC45.Saha, PThome, KCYamaguchi, RHou, ZWeremowicz, SDutta, AJ Biol Chem 273:18205-910757793Pubmed2000Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.Zou, LStillman, BMol Cell Biol 20:3086-967708676Pubmed1995Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast.Dalton, SWhitbread, LProc Natl Acad Sci U S A 92:2514-89335335Pubmed1997Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.Aparicio, OMWeinstein, DMBell, SPCell 91:59-6910518787Pubmed1999Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha.Kukimoto, IIgaki, HKanda, TEur J Biochem 265:936-4311296242Pubmed2001Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae.Kamimura, YTak, YSSugino, AAraki, HEMBO J 20:2097-10710430907Pubmed1999Differential assembly of Cdc45p and DNA polymerases at early and late origins of DNA replication.Aparicio, OMStout, AMBell, SPProc Natl Acad Sci U S A 96:9130-510790374Pubmed2000DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p.Tercero, JALabib, KDiffley, JFEMBO J 19:2082-93inferred by electronic annotationIEAGOIEADNA Replication Factor A (RPA) associates with the pre-replicative complex at the originDNA Replication Factor A (RPA) associates with the pre-replicative complex at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101887711Reactome DB_ID: 101887371RPA1-4 [nucleoplasm]RPA1-4Reactome DB_ID: 101887351UniProt:Q504I6rpa2UniProtQ504I61EQUAL270EQUALReactome DB_ID: 101887291UniProt:A5PMY4rpa3UniProtA5PMY41EQUAL121EQUALReactome DB_ID: 101887251UniProt:Q6NY74rpa1UniProtQ6NY742EQUAL616EQUALReactome DB_ID: 1018873311EQUAL261EQUALReactome Database ID Release 7510188737Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188737ReactomeR-DRE-685671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68567.1Reactome DB_ID: 101887731CDK:DDK:MCM10:active pre-replicative complex:CDC45:RPA1-4 [nucleoplasm]CDK:DDK:MCM10:active pre-replicative complex:CDC45:RPA1-4Reactome DB_ID: 101887711Reactome DB_ID: 101887371Reactome Database ID Release 7510188773Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188773ReactomeR-DRE-685681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68568.1Reactome Database ID Release 7510188778Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188778ReactomeR-DRE-689161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68916.1After pre-RC assembly and Cdc45 association with the origin of replication, Replication Protein A (RPA) also associates with chromatin. RPA is a heterotrimeric complex containing p70, p34, and p11 subunits, and also is required for DNA recombination and DNA repair. The p70 subunit of RPA binds to the primase subunits of Pol alpha:primase. The p70 and p34 subunits of RPA are phosphorylated in a cell cycle-dependent manner. RPA is a single-strand DNA (ssDNA) binding protein and its association with chromatin at this stage suggests that DNA is partially unwound. This suggestion has been confirmed by detection of ssDNA in budding yeast origins of replication using chemical methods.10882098Pubmed2000Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.Walter, JNewport, JMol Cell 5:617-279242902Pubmed1997Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.Wold, MSAnnu Rev Biochem 66:61-921311258Pubmed1992Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen.Dornreiter, IErdile, LFGilbert, IUvon Winkler, DKelly, TJEMBO J 11:769-7610473346Pubmed1999Replication protein A (RPA): the eukaryotic SSB.Iftode, CDaniely, YBorowiec, James ACrit Rev Biochem Mol Biol 34:141-802200738Pubmed1990Cell-cycle-regulated phosphorylation of DNA replication factor A from human and yeast cells.Din, SBrill, SJFairman, MPStillman, BGenes Dev 4:968-77inferred by electronic annotationIEAGOIEADNA polymerase alpha:primase binds at the originDNA polymerase alpha:primase binds at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 101886961DNA polymerase alpha:primase [nucleoplasm]DNA polymerase alpha:primaseReactome DB_ID: 101886841UniProt:B0S687pola2UniProtB0S6871EQUAL598EQUALReactome DB_ID: 101886801UniProt:E7FB68pola1UniProtE7FB681EQUAL1462EQUALReactome DB_ID: 101886941PRIM1:PRIM2 [nucleoplasm]PRIM1:PRIM2Reactome DB_ID: 101886921UniProt:B8JIP2prim2UniProtB8JIP21EQUAL509EQUALReactome DB_ID: 101886881UniProt:F1QKT6prim1UniProtF1QKT61EQUAL420EQUALReactome Database ID Release 7510188694Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188694ReactomeR-DRE-96688121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9668812.1Reactome Database ID Release 7510188696Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188696ReactomeR-DRE-685071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68507.1Reactome DB_ID: 101887141DNA polymerase epsilon:origin complex [nucleoplasm]DNA polymerase epsilon:origin complexReactome DB_ID: 684191Reactome DB_ID: 101887121DNA polymerase epsilon [nucleoplasm]DNA polymerase epsilonReactome DB_ID: 101887021Ghost homologue of POLE2 [nucleoplasm]Ghost homologue of POLE2Reactome DB_ID: 101887061UniProt:Q6PBL4pole3UniProtQ6PBL42EQUAL147EQUALReactome DB_ID: 101887101UniProt:F1RCI6pole4UniProtF1RCI62EQUAL117EQUALReactome DB_ID: 101887001UniProt:B0V351poleUniProtB0V3511EQUAL2286EQUALReactome Database ID Release 7510188712Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188712ReactomeR-DRE-684831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68483.1Reactome Database ID Release 7510188714Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188714ReactomeR-DRE-684851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68485.1Reactome DB_ID: 101887161DNA polymerase alpha:primase:DNA polymerase alpha:origin complex [nucleoplasm]DNA polymerase alpha:primase:DNA polymerase alpha:origin complexReactome DB_ID: 101886961Reactome DB_ID: 101887141Reactome Database ID Release 7510188716Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188716ReactomeR-DRE-685101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68510.1Reactome Database ID Release 7510188775Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188775ReactomeR-DRE-689141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68914.1DNA polymerase alpha:primase is comprised of four subunits, p180, p70, p58, and p49. The two primase subunits, p58 and p49, form a tight complex. The p49 subunit contains the DNA primase activity and one role of p58 appears to be tethering p49 to p180, the DNA polymerase catalytic subunit. The fourth subunit, p70, binds p180 and may tether the DNA polymerase alpha:primase complex to Cdc45.11395402Pubmed2002DNA primases.Frick, DNRichardson, CCAnnu Rev Biochem 70:39-808253737Pubmed1994Enzymatic characterization of the individual mammalian primase subunits reveals a biphasic mechanism for initiation of DNA replication.Copeland, WCWang, TSJ Biol Chem 268:26179-89inferred by electronic annotationIEAGOIEAACTIVATIONReactome Database ID Release 7510188776Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188776Reactome DB_ID: 10188773DNA polymerase epsilon binds at the originDNA polymerase epsilon binds at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 684191Reactome DB_ID: 101887121Reactome DB_ID: 101887141Reactome Database ID Release 7510188884Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10188884ReactomeR-DRE-689601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68960.1At the beginning of this reaction, 1 molecule of 'origin of replication', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon:origin complex' is present.<br><br> <br>inferred by electronic annotationIEAGOIEAACTIVATIONReactome DB_ID: 10188773Reactome Database ID Release 7510302837Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10302837ReactomeR-DRE-689621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68962.1GO0006270GO biological processIn S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding by Orc1 is unaffected by the association of ORC with origin DNA (ARS) sequences, but ATP hydrolysis is ARS-dependent, being suppressed by associated double-stranded DNA and stimulated by associated single-stranded DNA. These data are consistent with the hypothesis that ORC functions as an ATPase switch, hydrolyzing bound ATP and changing state as DNA unwinds at the origin immediately before replication. It is attractive to speculate that ORC likewise functions as a switch as human pre-replicative complexes are activated, but human Orc proteins are not well enough characterized to allow the model to be critically tested. mRNAs encoding human orthologs of all six Orc proteins have been cloned, and ATP-binding amino acid sequence motifs have been identified in Orc1, Orc4, and Orc5. Interactions among proteins expressed from the cloned genes have been characterized, but the ATP-binding and hydrolyzing properties of these proteins and complexes of them have not been determined.10970868Pubmed2000Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding.Lee, DGMakhov, AMKlemm, RDBell, SPEMBO J 19:4774-829829972Pubmed1999The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p.Tugal, TZou-Yang, XHGavin, KPappin, DCanas, BKobayashi, RHunt, TStillman, BJ Biol Chem 273:32421-911779870Pubmed2002Nuclear organization of DNA replication initiation proteins in mammalian cells.Fujita, MIshimi, YNakamura, HKiyono, TTsurumi, TJ Biol Chem 277:10354-6112169736Pubmed2002Orc6 involved in DNA replication, chromosome segregation, and cytokinesis.Prasanth, SGPrasanth, KVStillman, BScience 297:1026-319038340Pubmed1997Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex.Klemm, RDAustin, RJBell, SPCell 88:493-50210402192Pubmed1999latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant.Pinto, SQuintana, DGSmith, PMihalek, RMHou, ZHBoynton, SJones, CJHendricks, MVelinzon, KWohlschlegel, JAAustin, RJLane, WSTully, TDutta, ANeuron 23:45-5411323433Pubmed2001Assembly of the human origin recognition complex.Vashee, SSimancek, PChallberg, MDKelly, TJJ Biol Chem 276:26666-737502077Pubmed1996Conserved initiator proteins in eukaryotes.Gavin, KAHidaka, MStillman, BScience 270:1667-7110801458Pubmed2000ATPase switches controlling DNA replication initiation.Lee, DGBell, SPCurr Opin Cell Biol 12:280-511459976Pubmed2001ATP bound to the origin recognition complex is important for preRC formation.Klemm, RDBell, SPProc Natl Acad Sci U S A 98:8361-711395502Pubmed2001Architecture of the human origin recognition complex.Dhar, SKDelmolino, LDutta, AJ Biol Chem 276:29067-719353276Pubmed1997Identification of HsORC4, a member of the human origin of replication recognition complex.Quintana, DGHou, ZhThome, KCHendricks, MSaha, PDutta, AJ Biol Chem 272:28247-519765232Pubmed1998ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases.Quintana, DGThome, KCHou, ZHLigon, AHMorton, CCDutta, AJ Biol Chem 273:27137-45inferred by electronic annotationIEAGOIEA